CA2216963A1 - Tie-2 ligands, methods of making and uses thereof - Google Patents
Tie-2 ligands, methods of making and uses thereofInfo
- Publication number
- CA2216963A1 CA2216963A1 CA002216963A CA2216963A CA2216963A1 CA 2216963 A1 CA2216963 A1 CA 2216963A1 CA 002216963 A CA002216963 A CA 002216963A CA 2216963 A CA2216963 A CA 2216963A CA 2216963 A1 CA2216963 A1 CA 2216963A1
- Authority
- CA
- Canada
- Prior art keywords
- ligand
- tie
- nucleic acid
- receptor
- antibody
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000003446 ligand Substances 0.000 title claims abstract 53
- 238000000034 method Methods 0.000 title claims abstract 36
- 101100481408 Danio rerio tie2 gene Proteins 0.000 title 1
- 101100481410 Mus musculus Tek gene Proteins 0.000 title 1
- 150000007523 nucleic acids Chemical class 0.000 claims abstract 27
- 101000753291 Homo sapiens Angiopoietin-1 receptor Proteins 0.000 claims abstract 21
- 108020004707 nucleic acids Proteins 0.000 claims abstract 14
- 102000039446 nucleic acids Human genes 0.000 claims abstract 14
- 108010090091 TIE-2 Receptor Proteins 0.000 claims abstract 11
- 102000012753 TIE-2 Receptor Human genes 0.000 claims abstract 11
- 239000005557 antagonist Substances 0.000 claims abstract 9
- 102000005962 receptors Human genes 0.000 claims abstract 6
- 108020003175 receptors Proteins 0.000 claims abstract 6
- 102000044214 human TEK Human genes 0.000 claims abstract 5
- 239000000203 mixture Substances 0.000 claims abstract 5
- 230000012010 growth Effects 0.000 claims abstract 4
- 230000000903 blocking effect Effects 0.000 claims abstract 3
- 230000001737 promoting effect Effects 0.000 claims abstract 3
- 206010029113 Neovascularisation Diseases 0.000 claims abstract 2
- 210000004204 blood vessel Anatomy 0.000 claims abstract 2
- 230000004614 tumor growth Effects 0.000 claims abstract 2
- 102100022014 Angiopoietin-1 receptor Human genes 0.000 claims 16
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 13
- 210000004027 cell Anatomy 0.000 claims 8
- 241000124008 Mammalia Species 0.000 claims 5
- 241001465754 Metazoa Species 0.000 claims 5
- 239000013612 plasmid Substances 0.000 claims 5
- 239000003937 drug carrier Substances 0.000 claims 4
- 239000008194 pharmaceutical composition Substances 0.000 claims 4
- 108091026890 Coding region Proteins 0.000 claims 3
- 206010002961 Aplasia Diseases 0.000 claims 2
- 206010065553 Bone marrow failure Diseases 0.000 claims 2
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 claims 2
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 claims 2
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims 2
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims 2
- 239000013543 active substance Substances 0.000 claims 2
- 210000001185 bone marrow Anatomy 0.000 claims 2
- 150000001875 compounds Chemical class 0.000 claims 2
- 229940127089 cytotoxic agent Drugs 0.000 claims 2
- 239000002254 cytotoxic agent Substances 0.000 claims 2
- 231100000599 cytotoxic agent Toxicity 0.000 claims 2
- 238000003745 diagnosis Methods 0.000 claims 2
- 230000002068 genetic effect Effects 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 101100454807 Caenorhabditis elegans lgg-1 gene Proteins 0.000 claims 1
- 102000004127 Cytokines Human genes 0.000 claims 1
- 108090000695 Cytokines Proteins 0.000 claims 1
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 claims 1
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 claims 1
- 241000238631 Hexapoda Species 0.000 claims 1
- 102000015696 Interleukins Human genes 0.000 claims 1
- 108010063738 Interleukins Proteins 0.000 claims 1
- 108010025020 Nerve Growth Factor Proteins 0.000 claims 1
- 102000007072 Nerve Growth Factors Human genes 0.000 claims 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 239000000556 agonist Substances 0.000 claims 1
- 208000007502 anemia Diseases 0.000 claims 1
- -1 anti-VEGF antibody Proteins 0.000 claims 1
- 230000001580 bacterial effect Effects 0.000 claims 1
- 239000008280 blood Substances 0.000 claims 1
- 210000004369 blood Anatomy 0.000 claims 1
- 238000002512 chemotherapy Methods 0.000 claims 1
- 239000000430 cytokine receptor antagonist Substances 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 208000035475 disorder Diseases 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- 210000002889 endothelial cell Anatomy 0.000 claims 1
- 230000002708 enhancing effect Effects 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 230000002452 interceptive effect Effects 0.000 claims 1
- 208000028867 ischemia Diseases 0.000 claims 1
- 201000002364 leukopenia Diseases 0.000 claims 1
- 231100001022 leukopenia Toxicity 0.000 claims 1
- 210000004962 mammalian cell Anatomy 0.000 claims 1
- 210000000056 organ Anatomy 0.000 claims 1
- 229920001184 polypeptide Polymers 0.000 claims 1
- 102000004196 processed proteins & peptides Human genes 0.000 claims 1
- 108090000765 processed proteins & peptides Proteins 0.000 claims 1
- 230000002062 proliferating effect Effects 0.000 claims 1
- 102000004169 proteins and genes Human genes 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 claims 1
- 230000005855 radiation Effects 0.000 claims 1
- 239000002464 receptor antagonist Substances 0.000 claims 1
- 229940044551 receptor antagonist Drugs 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 206010043554 thrombocytopenia Diseases 0.000 claims 1
- 239000003053 toxin Substances 0.000 claims 1
- 231100000765 toxin Toxicity 0.000 claims 1
- 238000002054 transplantation Methods 0.000 claims 1
- 230000029663 wound healing Effects 0.000 claims 1
- 230000004069 differentiation Effects 0.000 abstract 2
- 230000001225 therapeutic effect Effects 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
- C07K14/515—Angiogenesic factors; Angiogenin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Vascular Medicine (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Obesity (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Steroid Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
The present invention provides for an isolated nucleic acid molecule encoding a human TIE-2 ligand. In addition, the invention provides for a receptor body which specifically binds a human TIE-2 ligand. The invention also provides an antibody which specifically binds a human TIE-2 ligand. The invention further provides for an antagonist of human TIE-2. The invention also provides for therapeutic compositions as well as a method of blocking blood vessel growth, a method of promoting neovascularization, a method of promoting the growth or differentiation of a cell expressing the TIE-2 receptor, a method of blocking the growth or differentiation of a cell expressing the TIE-2 receptor and a method of attenuating or preventing tumor growth in a human.
Claims (75)
1. An isolated nucleic acid molecule encoding a TlE-2 ligand.
2. An isolated nucleic acid molecule according to claim 1 wherein the nucleic acid sequence is:
(a) the nucleic acid sequence comprising the coding region of the human TlE-2 ligand as set forth in Figure 4 or Figure 5;
(b) a nucleic acid sequence that hybridizes under moderately stringent conditions to the nucleic acid sequence of (a) and which encodes a TlE-2 ligand that binds TlE-2 receptor; or (c) a nucleic acid sequence which, but for the degeneracy of the genetic code would hybridize to a nucleic acid sequence of (a) or (b), and which encodes a TlE-2 ligand that binds TlE-2 receptor.
(a) the nucleic acid sequence comprising the coding region of the human TlE-2 ligand as set forth in Figure 4 or Figure 5;
(b) a nucleic acid sequence that hybridizes under moderately stringent conditions to the nucleic acid sequence of (a) and which encodes a TlE-2 ligand that binds TlE-2 receptor; or (c) a nucleic acid sequence which, but for the degeneracy of the genetic code would hybridize to a nucleic acid sequence of (a) or (b), and which encodes a TlE-2 ligand that binds TlE-2 receptor.
3. An isolated nucleic acid molecule according to claim 2 wherein the encoded TlE-2 ligand is a TlE-2 agonist.
4. An isolated nucleic acid molecule according to claim 1 wherein the nucleic acid sequence is (a) the nucleic acid sequence comprising the coding region of the human TlE-2 ligand as set forth in Figure 6;
(b) the nucleic acid sequence comprising the coding region of the fibrinogen-like domain of the human TlE-2 ligand as set forth in Figure 4, 5 or 6;
(c) a nucleic acid sequence that hybridizes under moderately stringent conditions to the nucleic acid sequence of (a) and which encodes a TlE-2 ligand that binds TlE-2 receptor; or (d) a nucleic acid sequence which, but for the degeneracy of the genetic code would hybridize to a nucleic acid sequence of (a) or (b), and which encodes a TIE-2 ligand that binds TIE-2 receptor
(b) the nucleic acid sequence comprising the coding region of the fibrinogen-like domain of the human TlE-2 ligand as set forth in Figure 4, 5 or 6;
(c) a nucleic acid sequence that hybridizes under moderately stringent conditions to the nucleic acid sequence of (a) and which encodes a TlE-2 ligand that binds TlE-2 receptor; or (d) a nucleic acid sequence which, but for the degeneracy of the genetic code would hybridize to a nucleic acid sequence of (a) or (b), and which encodes a TIE-2 ligand that binds TIE-2 receptor
5. An isolated nucleic acid molecule according to claim 4 wherein the encoded TIE-2 ligand is a TIE-2 antagonist.
6. A vector which comprises a nucleic acid molecule of any one of the preceding claims.
7. A vector according to claim 6 wherein the nucleic acid molecule is operatively linked to an expression control sequence capable of directing its expression in a host cell.
8. A vector according to claim 6 or 7 which is a plasmid.
9. A plasmid according to claim 8 designated pJFE14 encoding TIE-2 ligand (ATCC Accession No. 75910).
10. A plasmid according to claim 8 designated pBluescript KS encoding human TIE-2 ligand 2 (ATCC Accession No. 75963).
11. A vector according to claim 6 or 7 designated as .lambda.gtlO encoding hTIE2 ligand 1 (ATCC Accession No. 75928).
12. An isolated TIE-2 ligand substantially free of other proteins.
13. An isolated TIE-2 ligand according to claim 12 encoded by a nucleic acid molecule according to claim 1.
14. An isolated TIE-2 ligand according to claim 12 encoded by a nucleic.
acid according to claim 2 or 3.
acid according to claim 2 or 3.
15. An isolated TIE-2 ligand according to claim 12 encoded by a nucleic acid according to claim 4 or 5.
16. A host-vector system for the production of a ligand according to any one of claims 12 to 15 which comprises a vector according to any one of claims 6 to 11 in a host cell.
17. A host-vector system according to claim 16 wherein the host cell is a bacterial, yeast, insect or mammalian cell.
18. A host vector system comprising the host vector system of claim 16 or 17 and a nucleic acid encoding the TIE-2 receptor.
19. A method of producing a ligand as defined in any one of claims 12 to 15 which comprises growing cells of a host-vector system according to any one of claims 16 to 18 under conditions permitting production of the ligand, and recovering the ligand so produced.
20. An antibody which specifically binds the ligand of any one of claims 12 to 15.
21. An antibody according to claim 20 which is a monoclonal antibody.
22. A receptorbody which specifically binds the ligand of any one of claims 12 to 15.
23. An isolated nucleic acid molecule encoding a receptorbody according to claim 22.
24. A vector comprising a nucleic acid molecule according to claim 23.
25. A vector according to claim 24 which is a plasmid.
26. A plasmid according to claim 25 designated vTIE-2 receptorbody (ATCC Deposit VR2484).
27. A conjugate comprising a ligand according to any one of claims 12 to 15 and, conjugated thereto, a cytotoxic agent.
28. A conjugate according to claim 27 wherein the cytotoxic agent is a radioisotope or toxin.
29. A pharmaceutical composition comprising a TIE-2 ligand according to any one of claims 12 to 15 and a pharmaceutically acceptable carrier.
30. A pharmaceutical composition comprising an antibody according to claim 20 or 21 and a pharmaceutically acceptable carrier.
31. A pharmaceutical composition comprising a receptorbody according to claim 22 and a pharmaceutically acceptable carrier.
32. A pharmaceutical composition comprising a conjugate according to claim 27 or 29 and a pharmaceutically acceptable carrier.
33. A ligand according to any one of claims 12 to 15, an antibody according to claim 20 or 21, a receptorbody according to claim 22, a conjugate according to claim 27 or 29, or a composition according to any one of claims 29 to 32 for use in a method of treatment of the human or animal body, or in a method of diagnosis.
34. A ligand according to claim 14 for use in a method of treatment of the human or animal body.
35. A ligand according to claim 15 for use in a method of treatment of the human or animal body.
36. An antibody or receptorbody according to claim 33, in which antibody or receptorbody specifically binds the ligand of claim 14, for use in a method of blocking blood vessel growth in a mammal.
37. An antibody or receptorbody according to claim 36 for use in a method wherein the mammal is a human.
38. A ligand according to claim 34 for use in a method of promoting neovascularization in a mammal.
39. A ligand according to claim 38 for use in the promotion of wound healing.
40. A ligand according to claim 38 for use in the treatment of ischemia.
41. A TIE-2 antagonist for use in a method of inhibiting TIE-2 ligand activity in a mammal.
42. An antagonist according to claim 41 which is an antibody capable of specifically binding TIE-2 receptor.
43. An antibody according to claim 42 which is an antibody according to claim 22 or 23.
44. An antagonist according to claim 42 which is a receptorbody according to claim 22.
45. An antagonist according to claim 41 which is a ligand according to claim 15.
46. An antagonist according to any one of claims 41 to 45 for use in a method wherein the mammal is a human.
47. An antagonist according to any one of claims 41 to 46 for use in a method of attenuating or preventing tumor growth in a human.
48. A method of maintaining a TIE-2 receptor expressing cell in culture, which method comprises administering to the TIE-2 receptor expressing cell an effective amount of the ligand of claim 14.
49. A method according to claim 48 wherein the TIE-2 receptor expressing cell is an endothelial cell.
50. A method of identifying a TIE-2 receptor antagonist comprising contacting cells expressing the TIE-2 receptor with: a) a test compound; and b) a ligand according to claim 14 or 15; under conditions permitting binding of the ligand to the receptor and determining whether the test compound is capable of interfering with the binding of the ligand to the receptor.
51. A polypeptide produced by the method of claim 19.
52. A nucleic acid according to claim 1 or 23, substantially as hereinbefore described with reference to any one of the foregoing Examples.
53. A vector according to claim 6 or 24, substantially as hereinbefore described with reference to any one of the foregoing Examples.
54. A ligand according to any one of claims 12 to 15, substantially as hereinbefore described with reference to any one of the foregoing Examples.
55. A host-vector system according to claim 16, substantially as hereinbefore described with reference to any one of the foregoing Examples.
56. A method according to claim 19, 48 or 50, substantially as hereinbefore described with reference to any one of the foregoing Examples.
57. An antibody according to claim 20 or 33, substantially as hereinbefore described.
58. A receptorbody according to claim 22 or 33, substantially as hereinbefore described with reference to any one of the foregoing Examples.
59. A conjugate according to claim 27 or 33, substantially as hereinbefore described.
60. A composition according to any one of claims 29 to 32 or 33, substantially as hereinbefore described with reference to any one of the foregoing Examples.
61. A TIE-2 antagonist according to claim 41, substantially as hereinbefore described with reference to any one of the foregoing Examples.
62. A ligandbody which specifically binds the TIE-2 receptor or the receptorbody of claim 22, 33 or 58.
63. A ligandbody which comprises a TIE-2 ligand fused to an immunoglobulin constant region.
64. The ligandbody of claim 63 wherein the TIE-2 ligand is TIE-2 ligand according to any one of claims 12 to 15 and the immunoglobulin constant region is the Fc portion of human lgG1.
65. A ligandbody according to any one of claims 62 to 64 for use in a method of treatment of the human or animal body, or in a method of diagnosis.
66. A method of treating a human or animal subject comprising administering to the subject an effective amount of a ligand according to any one of claims 12 to 15, an antibody according to claim 20 or 21, a receptorbody according to claim 22, a conjugate according to claim 27 or 28, a composition according to any one of claims 29 to 32, or a ligandbody according to any one of claims 62 to 65.
67. A method according to claim 66, the method being as defined in any one of claims 36 to 47.
68. A method according to claim 66 further comprising administering a second pharmaceutically active agent.
69. A method according to claim 68 wherein said second pharmaceutically active agent is a cytokine, neurotrophin, interleukin, cytokine antagonist, VEGF, anti-VEGF antibody, VEGF receptorbodies or bFGF.
70. A method of treating leukopenia comprising treating a patient with a therapeutically effective amount of the ligand according to claim 14.
71. A method of treating thrombocytopenia comprising treating a patient with a therapeutically effective amount of the ligand according to claim 14.
72. A method of treating anemia comprising treating a patient with a therapeutically effective amount of the ligand according to claim 14.
73. A method of enhancing bone marrow engraftment during transplantation comprising treating a patient with a therapeutically effective amount of the ligand according to claim 14.
74. A method of treating bone marrow aplasia or myelosuppression caused by radiation, chemical treatment or chemotherapy comprising treating a patient having such aplasia or myelosuppression with a therapeutically effective amount of the ligand according to claim 14.
75. A method of treating a proliferative disorder of a blood forming organ comprising treating a patient with a therapeutically effective amount of the ligand according to claim 15, an antibody according to claim 20 or 21, a receptorbody according to claim 22, a conjugate according to claim 27 or 28, a composition according to any one of claims 29 to 32, or a ligandbody according to any one of claims 62 to 65.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/418,595 US5814464A (en) | 1994-10-07 | 1995-04-06 | Nucleic acids encoding TIE-2 ligand-2 |
| US08/418,595 | 1995-04-06 | ||
| WOPCT/US95/12935 | 1995-06-10 | ||
| PCT/US1995/012935 WO1996011269A2 (en) | 1994-10-07 | 1995-10-06 | Tie-2 ligands, methods of making and uses thereof |
| PCT/US1996/004806 WO1996031598A1 (en) | 1995-04-06 | 1996-04-05 | Tie-2 ligands, methods of making and uses thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2216963A1 true CA2216963A1 (en) | 1996-10-10 |
| CA2216963C CA2216963C (en) | 2010-06-22 |
Family
ID=23658779
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2216963A Expired - Lifetime CA2216963C (en) | 1995-04-06 | 1996-04-05 | Tie-2 ligands, methods of making and uses thereof |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US6627415B1 (en) |
| EP (1) | EP0821728B1 (en) |
| JP (1) | JP4122056B2 (en) |
| AT (1) | ATE273384T1 (en) |
| AU (1) | AU715621B2 (en) |
| CA (1) | CA2216963C (en) |
| DE (1) | DE69633121T2 (en) |
| WO (1) | WO1996031598A1 (en) |
Families Citing this family (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE235551T1 (en) | 1996-06-19 | 2003-04-15 | Regeneron Pharma | LIGAND (TIE LIGAND-4) FROM TIE-2 RECEPTOR AND ITS USES |
| US6846914B2 (en) | 1996-06-19 | 2005-01-25 | Regeneron Pharmaceuticals, Inc. | Tie-2 ligand-3 |
| US6265564B1 (en) | 1996-08-02 | 2001-07-24 | Regeneron Pharmaceuticals, Inc. | Expressed ligand-vascular intercellular signalling molecule |
| NZ516848A (en) * | 1997-06-20 | 2004-03-26 | Ciphergen Biosystems Inc | Retentate chromatography apparatus with applications in biology and medicine |
| US6057435A (en) * | 1997-09-19 | 2000-05-02 | Genentech, Inc. | Tie ligand homologues |
| US5972338A (en) | 1997-09-19 | 1999-10-26 | Genentech, Inc. | Tie ligands homologues |
| US6350450B1 (en) | 1997-09-19 | 2002-02-26 | Genentech, Inc. | TIE ligand homologue antibody |
| US6030831A (en) * | 1997-09-19 | 2000-02-29 | Genetech, Inc. | Tie ligand homologues |
| US6348350B1 (en) | 1997-09-19 | 2002-02-19 | Genentech, Inc. | Ligand homologues |
| SV1999000069A (en) * | 1998-06-02 | 2000-04-11 | Lilly Co Eli | ANGIOPOYETIN RELATED TO SEQUENCE OF GEN 3 IN FACE SCAR REF. X-12261 |
| AU4320499A (en) * | 1998-06-02 | 1999-12-20 | Eli Lilly And Company | Angiopoietin related gene sequence scarface 1 |
| WO1999067382A2 (en) * | 1998-06-24 | 1999-12-29 | Compugen Ltd. | Angiopoietin-like growth factor sequences |
| AU774581B2 (en) * | 1998-08-31 | 2004-07-01 | New York University | Stem cells bearing an FGF receptor on the cell surface |
| DE69924009T2 (en) | 1998-12-23 | 2006-04-13 | Regeneron Pharmaceuticals, Inc. | METHOD FOR INCREASING THE BIOLOGICAL ACTIVITY OF LIGANDS |
| US6455035B1 (en) | 1999-03-26 | 2002-09-24 | Regeneron Pharmaceuticals, Inc. | Angiopoietins and methods of use thereof |
| ES2262518T5 (en) | 1999-06-07 | 2009-05-08 | Immunex Corporation | TEK ANTAGONISTS. |
| US6521424B2 (en) | 1999-06-07 | 2003-02-18 | Immunex Corporation | Recombinant expression of Tek antagonists |
| US7312325B2 (en) * | 2000-09-26 | 2007-12-25 | Duke University | RNA aptamers and methods for identifying the same |
| US7205275B2 (en) | 2001-10-11 | 2007-04-17 | Amgen Inc. | Methods of treatment using specific binding agents of human angiopoietin-2 |
| US7138370B2 (en) * | 2001-10-11 | 2006-11-21 | Amgen Inc. | Specific binding agents of human angiopoietin-2 |
| WO2003034990A2 (en) | 2001-10-25 | 2003-05-01 | Regeneron Pharmaceuticals, Inc. | Angiopoietins and methods of use thereof |
| JP4242590B2 (en) * | 2002-01-11 | 2009-03-25 | 俊一 塩澤 | Disease susceptibility genes for rheumatoid arthritis and use thereof |
| US7427594B1 (en) * | 2002-02-26 | 2008-09-23 | The Trustees Of The University Of Pennsylvania | Methods and pharmaceuticals compositions for treating coronary artery disease, ischemia,and vascular disease using angiopoietins |
| US7081443B2 (en) | 2002-05-21 | 2006-07-25 | Korea Advanced Institutes Of Science And Technology (Kaist) | Chimeric comp-ang1 molecule |
| AU2003297282A1 (en) | 2002-11-14 | 2004-06-15 | Cornell Research Foundation, Inc. | Protection of cardiac myocardium |
| US7871610B2 (en) * | 2003-08-12 | 2011-01-18 | Dyax Corp. | Antibodies to Tie1 ectodomain |
| US7485297B2 (en) * | 2003-08-12 | 2009-02-03 | Dyax Corp. | Method of inhibition of vascular development using an antibody |
| AU2004266242A1 (en) * | 2003-08-12 | 2005-03-03 | Dyax Corp. | Tie1-binding ligands |
| US8298532B2 (en) | 2004-01-16 | 2012-10-30 | Regeneron Pharmaceuticals, Inc. | Fusion polypeptides capable of activating receptors |
| DK2457578T3 (en) | 2004-09-28 | 2015-12-07 | Aprogen Inc | A chimeric molecule comprising angiopoietin-1 and a coiled-coil domain for use in the treatment of erectile dysfunction of the penis |
| CN101128483B (en) | 2004-12-21 | 2015-06-03 | 阿斯利康公司 | Angiopoietin-2 antibody and its application |
| CN106046166A (en) | 2006-04-07 | 2016-10-26 | 爱尔皮奥治疗有限公司 | Antibodies that bind to human protein tyrosine phosphatase [beta] (HPTP[beta]) and uses thereof |
| WO2008089070A2 (en) * | 2007-01-12 | 2008-07-24 | Dyax Corp. | Combination therapy for the treatment of cancer |
| US8507656B2 (en) | 2008-01-28 | 2013-08-13 | Medimmune Limited | Stabilized angiopoietin-2 antibodies and uses thereof |
| WO2009158432A2 (en) | 2008-06-27 | 2009-12-30 | Amgen Inc. | Ang-2 inhibition to treat multiple sclerosis |
| EP2714738B1 (en) | 2011-05-24 | 2018-10-10 | Zyngenia, Inc. | Multivalent and monovalent multispecific complexes and their uses |
| JP2014530244A (en) | 2011-10-13 | 2014-11-17 | エアピオ セラピューティックス， インコーポレイテッド | Methods for treating vascular leak syndrome and cancer |
| CA2907181C (en) | 2013-03-15 | 2023-10-17 | Viktor Roschke | Multivalent and monovalent multispecific complexes and their uses |
| HK1219836A1 (en) | 2013-03-15 | 2017-04-21 | Aerpio Therapeutics, Inc. | Compositions, formulations and methods for treating ocular diseases |
| US20150050277A1 (en) | 2013-03-15 | 2015-02-19 | Aerpio Therapeutics Inc. | Compositions and methods for treating ocular diseases |
| US9994560B2 (en) | 2014-03-14 | 2018-06-12 | Aerpio Therapeutics, Inc. | HPTP-β inhibitors |
| BR112017005730B1 (en) | 2014-09-26 | 2023-12-12 | Somalogic Operating Co., Inc | METHOD FOR SCREENING AN INDIVIDUAL FOR THE RISK OF A CARDIOVASCULAR EVENT OR FOR PREDICTING THE LIKELIHOOD THAT AN INDIVIDUAL WILL HAVE SUCH AN EVENT |
| CA2977578A1 (en) | 2015-03-04 | 2016-09-09 | Mesoblast International Sarl | Cell culture method for mesenchymal stem cells |
| WO2020068653A1 (en) | 2018-09-24 | 2020-04-02 | Aerpio Pharmaceuticals, Inc. | MULTISPECIFIC ANTIBODIES THAT TARGET HPTP - β (VE-PTP) AND VEGF |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5332671A (en) | 1989-05-12 | 1994-07-26 | Genetech, Inc. | Production of vascular endothelial cell growth factor and DNA encoding same |
| EP0550296A3 (en) | 1991-11-28 | 1993-12-29 | Terumo Corp | Vascular endothelial cells growth factor |
| US5955291A (en) | 1992-01-09 | 1999-09-21 | Alitalo; Kari | Antibodies recognizing tie receptor tyrosine kinase and uses thereof |
| AU4651893A (en) * | 1992-06-26 | 1994-01-24 | Immunex Corporation | Novel tyrosine kinase |
| US5643755A (en) | 1994-10-07 | 1997-07-01 | Regeneron Pharmaceuticals Inc. | Nucleic acid encoding tie-2 ligand |
| US5879672A (en) * | 1994-10-07 | 1999-03-09 | Regeneron Pharmaceuticals, Inc. | Tie-2 ligand 1 |
| US5814464A (en) * | 1994-10-07 | 1998-09-29 | Regeneron Pharma | Nucleic acids encoding TIE-2 ligand-2 |
| US5650490A (en) | 1994-10-07 | 1997-07-22 | Regeneron Pharmaceuticals, Inc. | Tie-2 ligand 2 |
-
1996
- 1996-04-05 JP JP53053796A patent/JP4122056B2/en not_active Expired - Lifetime
- 1996-04-05 DE DE69633121T patent/DE69633121T2/en not_active Expired - Lifetime
- 1996-04-05 WO PCT/US1996/004806 patent/WO1996031598A1/en not_active Ceased
- 1996-04-05 AT AT96910769T patent/ATE273384T1/en active
- 1996-04-05 EP EP96910769A patent/EP0821728B1/en not_active Expired - Lifetime
- 1996-04-05 CA CA2216963A patent/CA2216963C/en not_active Expired - Lifetime
- 1996-04-05 AU AU53871/96A patent/AU715621B2/en not_active Expired
-
1999
- 1999-11-18 US US09/442,717 patent/US6627415B1/en not_active Expired - Lifetime
Also Published As
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|---|---|
| DE69633121D1 (en) | 2004-09-16 |
| EP0821728B1 (en) | 2004-08-11 |
| JP4122056B2 (en) | 2008-07-23 |
| AU715621B2 (en) | 2000-02-03 |
| US6627415B1 (en) | 2003-09-30 |
| HK1008230A1 (en) | 1999-05-07 |
| AU5387196A (en) | 1996-10-23 |
| WO1996031598A1 (en) | 1996-10-10 |
| JPH11503323A (en) | 1999-03-26 |
| EP0821728A1 (en) | 1998-02-04 |
| ATE273384T1 (en) | 2004-08-15 |
| EP0821728A4 (en) | 1998-08-19 |
| DE69633121T2 (en) | 2005-07-28 |
| CA2216963C (en) | 2010-06-22 |
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